Vinyl alkyl isothiocyanates and their preparation



United States atent VINYL ALKYL ISDTHIO CYANATES AND THEIR PREPARATION Hein L. Klopping, Wilmington, DeL, assignor to E. I. du Pont de Nemours and Company, Wilmington, Del, a corporation of Delaware No Drawing. Application February 25, 1954, Serial No. 412,569

9 Claims. (Cl. 260-454) This invention relates to vinyl alkyl isothiocyanates containing a central sulfur atom, to a method for preparing them, and to fungicidal and insecticidal compositions containing them as active ingredients. More particularly, the invention is directed to vinyl mercapto alkyl isothiocyanates, vinyl sulfinyl alkyl isothiocyanates, and vinyl sulfonyl alkyl isothiocyanates.

The compounds of my invention can be represented by the following formula:

Where R1, R2 and R3 can be the same or difierent and represent hydrogen or an alkyl radical containing from 1 to 3 carbon atoms, Y is a divalent sulfur-containing group of the class consisting of S, SO, and S02, and n is an integer of from 2 to 6.

These compounds have some unique physical and biological properties. For example, in contrast to the bisisothiocyanates of the prior art, the sulfides, sulfoxides and Patented Mar. 12, 1957 The compound of Formula 1 can be prepared from known organic compounds by any of a variety of methods. For purposes of illustration, a schematic outline of a practical method of preparing compounds Where R1, R2 and Rs are hydrogen, n is 2 and Y is S, SO and S02 is shown hereafter. This method is, of course, applicable to all species falling within generic claim 1, and more about the individual steps in the generic process will appear later.

sulfones of the present invention are readily soluble in such inexpensive solvents as ethylene chloride, methylene chloride, acetone, methyl ethyl ketone, and benzene.

At concentrations higher than those which afford complete control of fungal diseases of plants and crops, the compounds of my invention exert an unusual type of herbicidal activity. Leaves treated with my novel compounds dehydrate and collapse but remain green. Consequently, the compounds are of use as pro-harvest dehydrating or wilting agents for grass and grain.

Illustrative compounds of the present invention are shown below. This list, however, is not in any way limitative.

1645 as being prepared from beta-mercaptoethylamine, ethylene chlorohydrin and hydrochloric acid.

Intermediates identified above as III, 'V and VIII are fully described and claimed in my copending application, Serial No. 412,659, filed concurrently herewith.

The compounds identified as IV, VI and IX are within the scope of the present invention. Of these three compounds, I prefer the sulfoxide (V) over the sulfide (III),

where R1, R2, R3 and n have the same significance as in Formula 1. f

The mercapto alcohols of Formula 2 may be prepared by a variety of known methods. One method comprises refluxing the chloro compound with NaSH in alcohol. An alternative method comprises the steps shown in the following diagram: 7

7' l CHsCOSIEI R2 Illa Rloos Coons In those instances where a compound of Formula 2 is to be prepared having R2 and R hydrogen and R1 alkyl, the synthesis steps are as follows:

The sulfur adds exclusively to the alpha carbon atom.

Compounds of Formula 2 wherein R3 is alkyl and R1 and R2 are hydrogen can be prepared in accordance with the scheme:

I. AeOOH I thiourea OIEtgC-H CH7CH R3 R: I A010 I H01 GE -CH AcOCH -C-H HOOH;C-H

\ Pyri S SAe SH Still other methods of preparing compounds of Formula 2- involve the use of olefins of the general formulae and, V

5. r n- I).

Olefins of Formula 4 yield mercapto alcohols of the formula V f a; nr-c i om'sn while those of Formula 5 yield a mixture of which components can be separated distillation.

The condensation is preferably carried out ina solvent in which both reactants are soluble such as, for example, a lower alkanol. ethanol is a particularly preferred solvent. The reaction proceeds well at the reflux temperature of ethanol. The by-product of the reaction, sodium chloride, can be removed by simple filtration.

The quantity of solvent may vary within rather wide limits but at least enough should be present such that stirring is not impeded by the precipitating sodium chloride.

The second step in my general process of preparing the products of this invention involves the replacement of a hydroxy group by chlorine. Any of several methods may be employed to effect this replacement. Compound I can, for example, be reacted with concentrated aqueous hydrochloric acid, preferably at a temperature slightly higher than the reflux temperature of concentrated hydrochloric acid, say, at about -160 C.

Alternatively, Compound 1,; or generically speaking, omega-chloroalkylaminehydrochloride, can be refluxed with thionyl chloride or phosphorus pentachloride in an organic solvent such as, for instance, chloroform. In these alternative methods protection of the free amino group by first converting it to an amine hydrochloride group by means of gaseous hydrogen chloride is advantageous but not essential.

The replacement of an amino group isothiocyanate.

However, when Compound II or an omega-chloroalkyl-omega-aminoalkyl sulfide hydrochloride is treated with thiophosgene and base, dehydrohalogenationdoes not take place. Dihydrohalogenation ot a S'alkylene 'Cl radical requires reflux temperatures, whichv can nothe applied in alkaline aqueous medium since the isothiocyano group is hydrolyzed under those circumstances.

by an isothiocyano' group is effected by use of CSClz and NaOH. This step If an excess of sodium group is intermediate between the corresponding sulfone and sulfide as regards ease of dehydrohalogenation.

Omega-chloroalkylsulfonylalkyl isothiocyanates, for example, the compound identified in the above scheme as VIII, can be isolated when the base used with thiophosgene is sodium bicarbonate rather than sodium hydroxide. The isolation is not essential, as already indicated, but is helpful in obtaining a sulfone of Formula 1 in high purity.

The oxidation of a sulfide of the formula where n, Rx, R2 and R3 have the same significance as in Formula 1, to the corresponding sulfoxide is preferably effected in acetic acid using hydrogen peroxide. For optimum yield the reaction mixture should be maintained at 2535 C., although satisfactory yields are obtained over a much wider range, say, from about 15 C. to the reflux temperature of acetic acid. It is preferred practice to dilute 30% hydrogen peroxide with approximately an equal volume of acetic acid and add this mixture dropwise to a solution of the aforementioned sulfide in acetic acid. The formation of tarry by-product can be substantially eliminated by avoiding an excess of hydrogen peroxide.

The oxidation of sulfide sulfur in a compound having the formula omega-chloroalkyl radical to a vinyl radical. In the case of beta-chloroethylsulfonyl radical, dehydrohalogenation .occurs almost instantly in any basic medium at ordinary temperatures, say, from 20 to 45 C. Illustrative of the basic media which can be used are aqueous sodium hydroxide, calcium carbonate in water, and barium carbonate in water.

For the dehydrohalogenation of the beta-chloroethylsulfinyl radical, and more particularly, forthe dehydrohalogenation of the beta-chloroethylmercapto radical, an-

hydrous conditions are required. Triethylamine in benzene is a satisfactory dehydrohalogenating agent for this purpose.

As indicated above, the compounds of my invention are readily soluble in chlorinated hydrocarbons such as, for instance, chloroform, methylene chloride, dichloroethane, and the like. They are also very soluble in benzene, toluene, acetone and methyl ethyl ketone. The sulfides of my invention are also soluble in aliphatic hydrocarbons, for example, n-heptane.

The compounds of the present invention are highly potent fungicides and insecticides. They are particularly useful in the control of fungus attack on seeds, plants, and vegetable crops and on other materials.

In order to better understand the nature of my invention, reference should be had to the following illustrative examples:

6 EXAMPLE 1 Preparation of isothiocyanic acid, 2-(vinylmercapto)ethyl ester To a solution of 368 g. of potassium hydroxide in 2 liters of ethyl alcohol there are added 219 g. of beta-mercaptoethanol. The solution is stirred and refluxed as 327 g. of beta-chloroethylamine hydrochloride, dissolved in 700 ml. of 95% ethyl alcohol, are added over a period of one hour. The reaction mixture is stirred for a period of 5 hours. After the mixture is allowed to stand overnight, it is filtered. The potassium chloride on the filter is washed with alcohol, and the filtrate is combined with the washings. The alcohol is removed from the filtrate by evaporation in vacuo, and the oil residue is distilled under a high vacuum. The fraction boiling at 120/0.9 mm. is collected and redistilled to give beta-aminoethyl-beta-hydroxyethyl sulfide. It is a colorless oil, B. P. 105-108/0.15 mm., n =1.5282.

A solution of beta-hydroxyethyl-beta-aminoethyl sul: fide in 1800 ml. of chloroform is stirred and heated to reflux. A solution of 357 grams of thionyl chloride in 220 ml. of chloroform is added dropwise. The reaction mixture is refluxed gently during the thionyl chloride addition. The addition takes three hours. After the reaction mixture has stood overnight, it is filtered. A solid is collected on a filter, washed with chloroform, and dried. This solid, which melts at 7779, consists essentially of beta-chloroethyl-beta-aminoethyl sulfide hydrochloride.

A solution of 17.6 g. of beta-chloroethyl-beta-aminoethyl sulfide hydrochloride in ml. of Water is cooled in ice. A solution of 11.5 g. of thiophosgene in 170 ml. of chloroform is added all at once. While the resulting mixture is stirred, a solution of 12 g. of sodium hydroxide in 60 ml. of water is added dropwisethe pH of the reaction mixture being kept below 7until the mixture no longer turns acidic on stopping the addition of base. Stirring of the reaction mixture is continued for a period of one hour. Then the chloroform layer is separated and combined with chloroform washings of the aqueous layer. The combined chloroform extract is dried over anhydrous sodium sulfate, treated with Darco, filtered and evaporated to dryness in vacuo. The oily residue is distilled in vacuo. The light yellow liquid boiling at 116-1l8/1 mm. which is collected is isothiocyanic acid, 2-(2-chloroethylmercapto)ethyl ester.

Analysis.Calcd. for CsHaNSzCl: C 33.05, H 4.43, N 7.71. Found: C 33.21, H 4.57, N 7.74.

A mixture of 18.1 g. of isothiocyanic acid, 2-(2-ch1oroethylmercapto)ethyl ester, 12 g. (20% excess) of anhydrous triethylamine, and 100 ml. of anhydrous benzene is refluxed on the steam bath for several days, until no more triethylamine hydrochloride separates. The mixture is filtered with suction, and the filtrate, after treatment with Darco, is vacuum concentrated to dryness. The residue, a brown oil, is extracted exhaustively with boiling chloroform. The insoluble tarry material is discarded, and the combined chloroform extracts are vacuum concentrated to dryness. The residue, at light brown oil, consists essentially of the 2-(vinylmercapto)ethyl ester of isothiocyanic acid.

EXAMPLE 2 Preparation of isothiocyanic acid, Z-(vinylsulfinyl) ethyl ester "The mixture is filteredv with suction. lected, treated with Darco .and vacuum concentrated to concentrated to dryness.

' period of five hours. Then the solution is vacuum con- 'the steam bath until no more triethylamine hydrochlo- About 14 hours of refluxing are required.

The filtrate is colride separates.

dryness. The residue, a brown oil, is exhaustively extracted with boiling ether. The insoluble tarry material is discarded and the combined ether extracts are vacuurn' concentrated to dryness. The residue, which is a light brownoil, is the desired product. The refractive index of this Z-(VinylSuIfinyDethyl ester of .isothiocyanic acid is n ='1.5862. its chemical analysis is as follows:

. Analysis.Calcd. for canousz: c 37.24, a 43s; Found: C 37.06, H 4.51.

'ethylsulfide hydrochloride (prepared .as in Example 1 in 600 ml. of water is stirred and cooled in an ethanolice mixture. A solution of 107 ml. of 40% .peracetic' acid in 600 ml; of water is added dropwise, the temperature of the reaction mixture being kept below 3 .C. The addition takes .75 minutes. Stirring of thereaction mixtureis continued for aperiod of one hour at temperatures 7 below 3 C. The'temperature is allowed to rise slow- 1y to room temperature while the mixture is stirred. This requires four additional hours; After the mix ture stands overnight, it is vacuum concentrated to .a

, syrup. This syrup is cooled in ice and rubbed with acetone until crystallization is complete. The oily crystals melt at 130440 C. After recrystallization from 400 mlrota'lzl mixture of absolute alcohol and 95% ethyl alcohol, these crystals or" beta-chloroethylebeta-aminoethylsulfone hydrochloride have a melting point of 153-155 C.

Analysisr -Calcd. for 'CtHiiOsNSCk C 23.08, H 5.28, N 6.73. Found: C 2326,11 5.33, N 6.72

A solution of 34 g. beta-chloroethylkbeta-arninoethylsulfonehydrochloridein 340 ml. of wateris stirred and cooled in ice. A solution of 14 ml. of thiophosgene in 340 ml. ofchloroform is added as a unit. Then a solution of 41 g. of sodium bicarbonate in 449 ml. of water is added dropwise over a period of three hours. The pH of the reaction mixture is kept below 7 at all time. The chloroform layer .is separated, combined with chloroform washings of the aqueous layer, dried over anhydrous sodium sulfate, treated with Darco, filtered, and vacuum The residue, a pale yellow oil, crystallizes on standing. The crystals are ground with n-hexane, an th hex ne-crystal i fi te ed- The crystals are collected and dried. The crystalline p hiocyanic acid. 2-(2-ch am thy ul 0ny ethyl-ester, melts at53.5e4 C.

Analysis.Calcd or CsI-IsOzNSzCl: C 28.10, 3.73, N 6.55, 3 30.31, Cl 16.59. Found: C 28.35, H 3.96, N 6.62, S 30.38, Cl 16.63. V V

To a solution of 16 g..of isothiocyanic acid, 2-(2- chloroethylsulfonyDethyl ester in 2.50 ml. of anhydrous benzene there is added a solutionof 7,9 g. (slight excess) anhydrous triethylarnine in 50 ml. of anhydrous benzone all at once. There is some heatevolution; Triethylamine hydrochloride separates promptly. After the mixture stands .for one hour, it is filtered with suction.

T he filtrate is vacuum concentrated to a brown oil.

oil is exhaustively extracted with boiling ether. Some insoluble, tarry .material is discarded, and the combined ether extracts are vacuum concentrated to dryness. The residue, a light yellow oil, crystallizes on cooling in ice. The crystals are ground with n-hexane, filtered off and dried. M. P. 38.540 C. Recrystallization from ethern-hexane raises the M. P. of' the desired isothiocyanic acid, Z-(Vinylsulfonyl) ethyl ester to 39:5-40 C. r

, Analysis.-Calcd. for C5H7O2NS2; C, 33.88, H 3.98, N 7.90. Found: C 34.28.1-1 4.09, N 7.95.

I claim: l. A compound having the formula nr-o=o r-(c m ..n=o.=s where R1, R2 and R3 are members-of the class'consisting of hydrogen and alkyl radicals having from 1 to 3 car'- bon atoms, Y is a divalent radical of the class consisting of 3, SO, and S02, and 'n is'an integer of from 2 to 6. 2. A compound of the formula R2 R3 i R C=CS--(CHz)n =G=S where R1, R2 ancLRs are members of the class consisting of hydrogen and ;alkyl radicals having from 1 to 3 carbon atoms, and n is an integer of from 2 to 6.

3. A compound of the formula R: 7 Rs V Rl'-'G=CSO-(GH2)n =C=S where R1, R2 and Ra'are members of the class consisting of hydrogenand alkyl radicals having from 1 'to 3 carbon atoms, and n is an integer'of from 2 to 6.

4. A compound of the formula a B2 Rs 7 V RI C=C'.SO2'(OHE)YF =.O.=s where 111, R2 and R3 are members of the class consisting of hydrogen and alkyl radicals having from '1 to 3 car bon atoms, and 'n-is an integer of from 2 to 6. V

. lsothiocyanic acid, 2- (vinylmercapto) -ethyl ester. isc-thiocyanic acid, Z-(VinylsuLlfinyD-ethylester. lsothiocyanic acid, '2-(vinyIsulfonyl)-ethyl ester. lsothiocyanic acid, Z-(propenylsultonyl)-ethyl ester. lsothiocyanic acid, 2 (isopropenylsulfonyl) ethyl ester.

References Cited in the file of this patent Schmid etaL: .Chein. Abst, vol. 42, page 7249 (1948). (Copy in Sci. 'Libraryi) 

1. A COMPOUND HAVING THE FORMULA 